PMID- 19923257
OWN - NLM
STAT- MEDLINE
DCOM- 20100407
LR  - 20100317
IS  - 1465-2099 (Electronic)
IS  - 0022-1317 (Linking)
VI  - 91
IP  - Pt 4
DP  - 2010 Apr
TI  - Immunodominant epitopes in nsp2 of porcine reproductive and respiratory syndrome 
      virus are dispensable for replication, but play an important role in modulation 
      of the host immune response.
PG  - 1047-57
LID - 10.1099/vir.0.016212-0 [doi]
AB  - Non-structural protein 2 (nsp2) of porcine reproductive and respiratory syndrome 
      virus (PRRSV) is the largest protein of this virus. In addition to its crucial 
      role in virus replication, recent studies have indicated its involvement in 
      modulating host immunity. In this study, each of the six identified 
      immunodominant nsp2 B-cell epitopes (ES2-ES7) was deleted using a type I PRRSV 
      cDNA infectious clone. Deletion of ES3, ES4 or ES7 allowed the generation of 
      viable virus. In comparison with the parental virus, the DeltaES3 mutant showed 
      increased cytolytic activity and more vigorous growth kinetics, whilst the 
      DeltaES4 and DeltaES7 mutants displayed decreased cytolytic activity and slower 
      growth kinetics in MARC-145 cells. These nsp2 mutants were characterized further 
      in a nursery pig disease model. The results showed that the DeltaES4 and DeltaES7 
      mutants exhibited attenuated phenotypes, whereas the DeltaES3 mutant produced a 
      higher peak viral load in pigs. The antibody response reached similar levels, as 
      measured by IDEXX ELISA at 21 days post-infection, and slightly higher levels of 
      mean virus neutralizing titres were observed from pigs infected by the DeltaES4 
      and DeltaES7 mutants. The expression of innate and T-helper 1 cytokines was 
      measured in peripheral blood mononuclear cells or virus-infected macrophages. The 
      results consistently showed that interleukin-1beta and tumour necrosis factor 
      alpha expression levels were downregulated in cells that were stimulated (or 
      infected) with the DeltaES3 mutant compared with parental virus and the other 
      nsp2 deletion mutants. These results suggest that certain regions in nsp2 are 
      non-essential for PRRSV replication but may play an important role in modulation 
      of host immunity in vivo.
FAU - Chen, Zhenhai
AU  - Chen Z
AD  - Veterinary Science Department, South Dakota State University, Brookings, SD 
      57007, USA.
FAU - Zhou, Xiaoxin
AU  - Zhou X
FAU - Lunney, Joan K
AU  - Lunney JK
FAU - Lawson, Steven
AU  - Lawson S
FAU - Sun, Zhi
AU  - Sun Z
FAU - Brown, Elizabeth
AU  - Brown E
FAU - Christopher-Hennings, Jane
AU  - Christopher-Hennings J
FAU - Knudsen, David
AU  - Knudsen D
FAU - Nelson, Eric
AU  - Nelson E
FAU - Fang, Ying
AU  - Fang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20091118
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (Antibodies, Viral)
RN  - 0 (Cytokines)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Viral/blood
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis/genetics
MH  - Immunity, Innate
MH  - *Immunodominant Epitopes
MH  - Molecular Sequence Data
MH  - Porcine Reproductive and Respiratory Syndrome/*immunology
MH  - Porcine respiratory and reproductive syndrome virus/growth & 
      development/*immunology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Swine
MH  - Viral Nonstructural Proteins/*immunology
MH  - *Virus Replication
EDAT- 2009/11/20 06:00
MHDA- 2010/04/08 06:00
CRDT- 2009/11/20 06:00
PHST- 2009/11/20 06:00 [entrez]
PHST- 2009/11/20 06:00 [pubmed]
PHST- 2010/04/08 06:00 [medline]
AID - vir.0.016212-0 [pii]
AID - 10.1099/vir.0.016212-0 [doi]
PST - ppublish
SO  - J Gen Virol. 2010 Apr;91(Pt 4):1047-57. doi: 10.1099/vir.0.016212-0. Epub 2009 
      Nov 18.